Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Antihypertensive treatment may have reduced the rate of dementia in older patients with isolated systolic hypertension

ACP J Club. 1999 May-June;130:57. doi:10.7326/ACPJC-1999-130-3-057


Source Citation

Forette F, Seux ML, Staessen JA, et al., for the Syst-Eur Investigators. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998 Oct 24; 352:1347-51.


Abstract

Question

In older patients with isolated systolic hypertension, can antihypertensive treatment prevent dementia?

Design

Randomized, double-blind, placebo-controlled trial with up to 5 years of follow-up (an optional project in the Systolic Hypertension in Europe [Syst-Eur] trial).

Setting

106 centers in Europe.

Patients

2470 patients who were ≥ 60 years of age and had systolic blood pressure (BP) (when seated) 160 to 219 mm Hg and diastolic BP < 95 mm Hg. 2418 patients (98%) were analyzed (mean age 70 y, 66% women).

Intervention

After stratification by sex, center, and previous cardiovascular complications, patients were allocated to antihypertensive treatment (n = 1238) or matching placebo (n = 1180). The goal of antihypertensive treatment was to reduce systolic BP by ≥ 20 mm Hg or to achieve BP < 150 mm Hg. Treatment was started with nitrendipine, 10 to 40 mg/d. If necessary, nitrendipine was combined or replaced with enalapril, 5 to 20 mg/d; hydrochlorothiazide, 12.5 to 25 mg/d; or both drugs.

Main outcome measure

Incidence of dementia assessed by using the Diagnostic and Statistical Manual of Mental Disorders, 3d edition, Revised (DSM-III-R).

Main results

Analysis was by intention to treat. The Syst-Eur trial was stopped early according to preset rules because antihypertensive treatment reduced incidence of stroke more than did placebo. After a median follow-up of 2 years, 11 new cases of dementia (8 Alzheimer and 3 mixed) occurred in the antihypertensive treatment group, and 21 new cases (15 Alzheimer, 4 mixed, and 2 vascular) occurred in the placebo group {P = 0.06}* (Table). Time-to-event analysis showed that antihypertensive treatment reduced the rate of dementia more than placebo (3.8 vs 7.7 cases per 1000 person-y, P = 0.05).

Conclusion

In older patients with isolated systolic hypertension, antihypertensive treatment may have led to a reduction in dementia.

Sources of funding: Bayer AG; Belgian National Research Fund; Specia SA; INSERM. Drugs supplied by Bayer AG and Merck, Sharpe, and Dohme.

For correspondence: Professor F. Forette, Department of Geriatrics, Hôpital Broca, CHU Cochin, Université Paris V, 54-56 rue Pascal, 75013 Paris, France. FAX 33-44-08-35-10.

*P value calculated from data in article.


Table. Antihypertensive treatment vs placebo in older patients with systolic hypertension at a median follow-up of 2 years†

Outcome Antihypertensive treatment Placebo RRR (95% CI) NNT (CI)
Dementia 0.8% 1.8% 50.1% (-1.5 to 75.5) Not significant

†Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

Systolic hypertension and dementia are common, especially in the oldest-old (persons ≥ 85 years of age). The possibility that treatment of systolic hypertension reduces the incidence of vascular dementia was a research question of the Syst-Eur trial in 1991 (1). Forette and colleagues attempted to answer a broader question involving all forms of dementia: Alzheimer, mixed, and vascular.

With respect to the original question, only 2 cases of vascular dementia occurred—far less than originally predicted (1). The claim that treatment of systolic hypertension reduced the incidence of all types of dementia by 50% may constitute a trend, although given that the CI around this estimate included zero, the data are also compatible with no treatment effect. Because these results constitute a post hoc analysis, a false-positive result is possible. The only other comparable study (2) showed no protection against dementia with control of systolic hypertension, although different drugs were used.

Even if the authors' hypothesis is correct, the safety of calcium-channel blockers, especially in the elderly, has been recently questioned (3). The generalizability of this efficacy trial is limited because only relatively young patients with few comorbid conditions were included.

What are the clinical implications? The exact question initially posed in 1991 was not answered here. The evidence is intriguing and offers hope, but at this stage, nothing more. Enough good reasons (beyond dementia prevention) exist to treat systolic hypertension, at least in persons < 85 years of age. For the oldest old persons with hypertension and especially those with comorbid conditions, the jury is still out.

A. Mark Clarfield, MD
Sarah Herzog Memorial Hospital
Ora Paltiel, MD
Hadassah Medical CentreJerusalem, Israel

A. Mark Clarfield, MD
Sarah Herzog Memorial Hospital
Jerusalem, Israel

Ora Paltiel, MD
Hadassah Medical Centre
Jerusalem, Israel


References

1. Forette F, Amery A, Staessen J, et al. Is prevention of vascular dementia possible? The Syst-Eur Vascular Dementia Project. Aging (Milano). 1991;3:373-82.

2. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265:3255-64.

3. Opie LH. Calcium channel blockers for hypertension: dissecting the evidence for adverse effect. Am J Hypertens. 1997;10:565-77.